Human stress-inducible Hsp70 has a high propensity to form ATP dependent antiparallel dimers that are differentially regulated by cochaperone binding

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F19%3A00078090" target="_blank" >RIV/00209805:_____/19:00078090 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/19:00109067 RIV/00216208:11310/19:10395404

Výsledek na webu

<a href="http://www.mcponline.org/content/early/2018/11/20/mcp.RA118.001044.long" target="_blank" >http://www.mcponline.org/content/early/2018/11/20/mcp.RA118.001044.long</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/mcp.RA118.001044" target="_blank" >10.1074/mcp.RA118.001044</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Human stress-inducible Hsp70 has a high propensity to form ATP dependent antiparallel dimers that are differentially regulated by cochaperone binding

Popis výsledku v původním jazyce

Eukaryotic protein homeostasis (proteostasis) is largely dependent on the action of highly conserved Hsp70 molecular chaperones. Recent evidence indicates that, apart from conserved molecular allostery, Hsp70 proteins have retained and adapted the ability to assemble as functionally relevant ATP-bound dimers throughout evolution. Here, we have compared the ATP-dependent dimerization of DnaK, human stress-inducible Hsp70, Hsc70 and BiP Hsp70 proteins, showing that their dimerization propensities differ, with stress-inducible Hsp70 being predominantly dimeric in the presence of ATP. Structural analyses using hydrogen/deuterium exchange mass spectrometry, native electrospray ionization mass spectrometry and small-angle X-ray scattering revealed that stress-inducible Hsp70 assembles in solution as an antiparallel dimer with the intermolecular interface closely resembling the ATP-bound dimer interfaces captured in DnaK and BiP crystal structures. ATP-dependent dimerization of stress-inducible Hsp70 is necessary for its efficient interaction with Hsp40, as shown by experiments with dimerization-deficient mutants. Moreover, dimerization of ATP-bound Hsp70 is required for its participation in high molecular weight protein complexes detected ex vivo, supporting its functional role in vivo. As human cytosolic Hsp70 has the ability to interact with tetratricopeptide repeat (TPR) domain containing co-chaperones, we tested the interaction of Hsp70 ATP-dependent dimers with Chip and Tomm34 co-chaperones. While Chip associates with intact Hsp70 dimers to form a larger complex, binding of Tomm34 disrupts the Hsp70 dimer and this event plays an important role in Hsp70 activity regulation. In summary, this study provides structural evidence of robust ATP-dependent antiparallel dimerization of human inducible Hsp70 protein and suggests a novel role of TPR domain co-chaperones in multichaperone complexes involving Hsp70 ATP-bound dimers.

Název v anglickém jazyce

Human stress-inducible Hsp70 has a high propensity to form ATP dependent antiparallel dimers that are differentially regulated by cochaperone binding

Popis výsledku anglicky

Eukaryotic protein homeostasis (proteostasis) is largely dependent on the action of highly conserved Hsp70 molecular chaperones. Recent evidence indicates that, apart from conserved molecular allostery, Hsp70 proteins have retained and adapted the ability to assemble as functionally relevant ATP-bound dimers throughout evolution. Here, we have compared the ATP-dependent dimerization of DnaK, human stress-inducible Hsp70, Hsc70 and BiP Hsp70 proteins, showing that their dimerization propensities differ, with stress-inducible Hsp70 being predominantly dimeric in the presence of ATP. Structural analyses using hydrogen/deuterium exchange mass spectrometry, native electrospray ionization mass spectrometry and small-angle X-ray scattering revealed that stress-inducible Hsp70 assembles in solution as an antiparallel dimer with the intermolecular interface closely resembling the ATP-bound dimer interfaces captured in DnaK and BiP crystal structures. ATP-dependent dimerization of stress-inducible Hsp70 is necessary for its efficient interaction with Hsp40, as shown by experiments with dimerization-deficient mutants. Moreover, dimerization of ATP-bound Hsp70 is required for its participation in high molecular weight protein complexes detected ex vivo, supporting its functional role in vivo. As human cytosolic Hsp70 has the ability to interact with tetratricopeptide repeat (TPR) domain containing co-chaperones, we tested the interaction of Hsp70 ATP-dependent dimers with Chip and Tomm34 co-chaperones. While Chip associates with intact Hsp70 dimers to form a larger complex, binding of Tomm34 disrupts the Hsp70 dimer and this event plays an important role in Hsp70 activity regulation. In summary, this study provides structural evidence of robust ATP-dependent antiparallel dimerization of human inducible Hsp70 protein and suggests a novel role of TPR domain co-chaperones in multichaperone complexes involving Hsp70 ATP-bound dimers.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular &amp; cellular proteomics : MCP

ISSN

1535-9476

e-ISSN

—

Svazek periodika

18

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

320-337

Kód UT WoS článku

000457454000011

EID výsledku v databázi Scopus

2-s2.0-85060950648